Epstein-Barr virus expression in Hodgkin's disease: Correlation with histologic subtypes and T and B lymphocyte distribution

Background: The pathogenesis of Hodgkin's disease (HD) has been linked to E pstein-Barr virus (EBV). Some histologic subtypes show a high level of vira l expression, These include mixed cellularity (MCHD) and nodular sclerosis (NSHD) subtypes. Grade II NSHD is a more aggressive variant of HD. Lymphocy te predominant (LPHD) is a B cell lymphoproliferative disorder that has not been associated with EBV expression. Infiltrating lymphocytes in HD are pr edominantly T lymphocytes, with a minor component of B lymphocytes. In the current study, EBV expression was tested in cases of HD in relation to hist ologic subtypes, An attempt was made at correlating EBV expression with T a nd B lymphocyte distribution in lymph nodes involved by HD. Method: Formalin-fixed paraffin-embedded tissue from 62 cases of HD were te sted for EBV mRNA expression, using the EBER-1 probe and in situ hybridizat ion. T and B lymphocyte distribution and their ratios were evaluated using antibodies to T and B lymphocytes (UCHL-1 [CD45 RQ] and CD 20, respectively ), and the immunoperoxidase technique. Results: The cases were seen in 38 male and 24 female patients, with an age range of 3 to 72 pears (median 25 years). Then were 30 cases of grade I an d 15 cases of grade II NSHD, 9 cases of MCHD and 8 cases of LPHD. EBV mRNA expression was seen in 29 cases (46%). This expression was seen in 8 cases of grade I NSHD (26%). 13 cases of grade II NSHD (86%) and 8 cases of MCHD (88%). None of the cases of LPI ID showed viral expression. T to B lymphocy te ratios in EBV-positive cases ranged from 1/6 to 8/1, and ranged from 2/1 to 20/1 in EBV-negative cases (P=0.06), Nine of the 29 positive cases (31% ) showed equal T/B lymphocyte ratios (n=4), or predominance of B lymphocyte s (n=5). None of the EBV-negative cases showed predominance of B lymphocyte s. Conclusion: Our study confirms previously reported findings of the prevalen ce of EBV expression in MCHD and NSHD. Our findings also suggest that EBV e xpression may be more commonly seen in aggressive forms of HD. Decreased nu mbers of T lymphocytes in these aggressive subtypes may suggest that a proc ess of more profound T lymphocyte depletion is occurring in these cases, le ading to uncontrolled EBV replication and more aggressive disease.